Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed postmenopausal NCI NCCTG-933253 NCCTG-93-32-53

Objectives

I.  Evaluate in concurrent Phase II trials the response rate, duration of 
response, time to progression, survival, and toxicity of 2 doses of the 
aromatase inhibitor letrozole in women with metastatic breast cancer who have 
failed prior hormonal therapy.

Entry Criteria

Disease Characteristics:

Histologically or cytologically confirmed breast cancer

Progressive metastatic disease required
  No brain metastases
  No hepatic metastases involving more than one-third of the
     liver

Histologic confirmation not required for the following:
  Multiple pulmonary nodules known to be new or progressive
  Unequivocal radiographic evidence of multiple bone metastases

Failure on prior hormonal therapy required
  Disease recurrence within 12 months of the last dose of
  tamoxifen administered as adjuvant therapy is considered
  treatment failure

Measurable or evaluable disease required, e.g.:
  Bidimensionally measurable lesion

  Unidimensionally measurable hepatomegaly

Lesion assessable but not measurable on radiograph (e.g.,
mediastinal masses, pleural-based masses, or lytic bone
metastasis) or photograph (e.g., soft tissue and skin
metastases)

Pleural effusions, ascites, and blastic metastases are not
considered measurable or evaluable

Hormone receptor status:
  ER- and/or PgR-positive (i.e., at least 10 fmoles/mg of
  cytosol protein) or unknown
     Immunohistochemistry determinations may be defined
     according to institutional standards

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  Prior adjuvant chemotherapy allowed
  No more than 1 prior chemotherapy for metastatic disease

Endocrine therapy:
  No more than 2 prior hormonal therapies
  No prior aromatase inhibition therapy, i.e.:
     No aminoglutethimide
     No 4-hydroxyandrostenedione
     No fadrozole
     No letrozole
     No other recognized aromatase inhibitor agents
  No prior adrenalectomy or hypophysectomy

Radiotherapy:
  Not specified

Surgery:
  Not specified

Patient Characteristics:

Age:
  Not specified

Menopausal status:
  Postmenopausal as determined by 1 of the following:
     More than 12 months since LMP
     Between 4 and 12 months since LMP with follicle-
        stimulating hormone in postmenopausal range
     Prior oophorectomy
     Hysterectomy without oophorectomy (follicle-stimulating
        hormone in postmenopausal range if age 60 or under)

Sex:
  Female only

Performance status:
  ECOG 0-2

Hematopoietic:
  WBC greater than 2,000
  Platelets greater than 75,000

Hepatic:
  Bilirubin less than 0.8 mg/dl above ULN

Renal:
  Creatinine less than 1 mg/dl above ULN
  Calcium less than 10% above ULN

Blood/body fluid analyses to determine eligibility and imaging
studies and physical exams for tumor measurement completed
within 14 days prior to registration

Expected Enrollment

Each arm is considered an independent Phase II study, and up to 45 
patients/arm will be accrued over 6-12 months.  If none of the first 15 or no 
more than 1 of the first 30 patients treated on a given arm responds, accrual 
to that arm will cease.

Outline

Randomized study.

Arm A:  Aromatase Inhibition Therapy.  Letrozole.  Low dose.

Arm B:  Aromatase Inhibition Therapy.  Letrozole.  High dose.

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

James Ingle, MD, Protocol chair		Ph: 507-284-8432 Email: ingle.james@mayo.edu